Beneficial effects of evodiamine on P2X4-mediated inflammatory injury of human umbilical vein endothelial cells due to high glucose

• Chronic high glucose up-regulates the expression of P2X4 receptor in HUVECs.
• Evodiamine inhibits high glucose-induced expression of P2X4R in HUVECs.
• Evodiamine inhibits high glucose-induced expression of NF-κB, TNFR-ɑ in HUVECs.
• Evodiamine decreases high glucose-induced the production of ROS in HUVECs.
• Evodiamine increases the production of NO in HUVECs.

Evodiamine has been reported to exhibit anti-inflammatory and anti-nociceptive effects, but the underlying mechanisms remain to be defined. P2X4 receptor (P2X4R) is a subtype of ATP receptors and plays important roles in pain, inflammatory and immune responses. We aimed to investigate whether evodiamine has beneficial effects on endothelial inflammatory injury mediated by chronic high glucose condition. We found that culturing human umbilical vein endothelial cells (HUVECs) with high glucose significantly increased the expression of P2X4 receptor in HUVECs, cytosolic Ca2 + concentrations and intracellular reactive oxygen species (ROS) while decreasing nitric oxide (NO); these effects could be reversed by evodiamine. High glucose also significantly increased the expression of the pro-inflammatory activators (NF-κB) and TNFR-ɑ, which was accompanied by the elevation of P2X4R levels. Evodiamine was able to down-regulate the elevated NF-κB, TNFR-ɑ, P2X4R and ROS, and up-regulate the decreased NO. Thus the evodiamine may exert the anti-inflammation activity on high-glucose challenge HUVEC via suppressing the P2X4R signaling pathway, exhibiting beneficial ability to protect HUVECs from glucotoxicity.